Machine learning in bail decisions and judges' trustworthiness.

The use of AI algorithms in criminal trials has been the subject of very lively ethical and legal debates recently. While there are concerns over the lack of accuracy and the harmful biases that certain algorithms display, new algorithms seem more promising and might lead to more accurate legal decisions. Algorithms seem especially relevant for bail decisions, because such decisions involve statistical data to which human reasoners struggle to give adequate weight. While getting the right legal outcome is a strong desideratum of criminal trials, advocates of the relational theory of procedural justice give us good reason to think that fairness and perceived fairness of legal procedures have a value that is independent from the outcome. According to this literature, one key aspect of fairness is trustworthiness. In this paper, I argue that using certain algorithms to assist bail decisions could increase three different aspects of judges' trustworthiness: (1) actual trustworthiness, (2) rich trustworthiness, and (3) perceived trustworthiness.

Factors Influencing Fourth-Year Pharmacy Students' Decisions to Pursue a Hospital Pharmacy Residency.

BACKGROUND: The Canadian Society of Hospital Pharmacists promotes the recruitment of residency-trained pharmacists for work in hospitals and related health care settings. However, Quebec hospitals are still hiring non-residency trained pharmacists, in part because of a severe shortage of hospital pharmacists. To date, no studies have examined the factors influencing the career choices of fourth-year pharmacy students in Canada. OBJECTIVES: To identify motivating factors and barriers influencing students' decision to pursue a hospital pharmacy residency. METHODS: All 186 fourth-year students in the Faculty of Pharmacy, Université de Montréal, were invited by e-mail to participate in a validated and institutionally approved survey that was available online between March and May 2014. RESULTS: Of the 138 respondents who returned a completed survey (74% response rate), 36 (26%) planned to apply for a hospital pharmacy residency. Those planning to apply for a residency were older (p = 0.037) and had more hospital work experience (36% versus 3%, p < 0.001) than those not planning to apply. The most important motivators for pursuing a residency were potential gains in knowledge (reported by 88% of respondents, whether or not they were planning to pursue a residency), experience (80%), and self-confidence (62%). The most frequently reported barriers were recognition that a hospital pharmacy residency is a highly demanding program (65%), having work available upon graduation from the undergraduate program (43%), and financial obligations (34%). Hospital experiential rotations influenced, either positively or negatively, 23 (72%) of the 32 students who changed their decision to pursue or not pursue residency training over the course of their studies. CONCLUSIONS: The potential gain in knowledge and experience acquired through residency, the fact that it is considered a highly demanding program, and having work available upon graduation from undergraduate studies were the most influential factors in fourth-year pharmacy students' decision of whether to pursue a hospital pharmacy residency.

CONTEXTE: La Société canadienne des pharmaciens d'hôpitaux encourage les établissements de santé à embaucher des pharmaciens qui ont fait une résidence. Or, les hôpitaux du Québec continuent d'embaucher des pharmaciens dénués de cette formation, entre autres à cause d'une importante pénurie de pharmaciens hospitaliers. À ce jour, aucune étude n'a examiné les facteurs qui influencent les choix de carrière des étudiants en quatrième année de pharmacie au Canada. OBJECTIFS: Découvrir les facteurs qui motivent les étudiants à faire une résidence en pharmacie d'hôpital et les facteurs qui les en dissuadent. MÉTHODES: L'ensemble des 186 étudiants en quatrième année à la Faculté de pharmacie de l'Université de Montréal ont été invités par courriel à participer à un sondage validé, approuvé par l'établissement, qui était disponible en ligne entre mars et mai 2014. RÉSULTATS: Parmi les 138 répondants ayant rempli et retourné le sondage (taux de réponse de 74 %), 36 (26 %) avaient l'intention de s'inscrire à la résidence en pharmacie d'hôpital. Ces derniers étaient plus âgés (p = 0,037) et possédaient une plus grande expérience de travail en hôpital (36 % contre 3 %, p < 0,001) que ceux qui n'envisageaient pas de s'inscrire à la résidence. Les facteurs qui motivaient le plus tous les répondants (dont ceux qui ne planifiaient pas faire une résidence) à entreprendre une résidence étaient la possibilité : d'acquérir les connaissances (88 %), de gagner de l'expérience (80 %) et d'augmenter la confiance en soi (62 %). Les facteurs qui dissuadaient le plus souvent l'ensemble des répondants étaient : la conviction que la résidence en pharmacie d'hôpital est un programme très exigeant (65 %), l'accès à un travail dès qu'ils obtiennent le diplôme de premier cycle (43 %) et les obligations financières (34 %). Les stages en milieu hospitalier ont influencé, positivement ou négativement, 23 (72 %) des 32 étudiants qui ont changé d'idée quant à la poursuite ou non d'une résidence pendant leurs études. CONCLUSIONS: La possibilité d'acquérir des connaissances et de l'expérience grâce à la résidence, le fait que le programme soit considéré comme très exigeant et l'accès à un emploi dès l'obtention du diplôme de premier cycle : ces facteurs influençaient le plus le choix des étudiants en quatrième année pour ce qui est d'entreprendre ou non une résidence en pharmacie d'hôpital.

Requirement of NOX2 and reactive oxygen species for efficient RIG-I-mediated antiviral response through regulation of MAVS expression.

The innate immune response is essential to the host defense against viruses, through restriction of virus replication and coordination of the adaptive immune response. Induction of antiviral genes is a tightly regulated process initiated mainly through sensing of invading virus nucleic acids in the cytoplasm by RIG-I like helicases, RIG-I or Mda5, which transmit the signal through a common mitochondria-associated adaptor, MAVS. Although major breakthroughs have recently been made, much remains unknown about the mechanisms that translate virus recognition into antiviral genes expression. Beside the reputed detrimental role, reactive oxygen species (ROS) act as modulators of cellular signaling and gene regulation. NADPH oxidase (NOX) enzymes are a main source of deliberate cellular ROS production. Here, we found that NOX2 and ROS are required for the host cell to trigger an efficient RIG-I-mediated IRF-3 activation and downstream antiviral IFNbeta and IFIT1 gene expression. Additionally, we provide evidence that NOX2 is critical for the expression of the central mitochondria-associated adaptor MAVS. Taken together these data reveal a new facet to the regulation of the innate host defense against viruses through the identification of an unrecognized role of NOX2 and ROS.

Respiratory syncytial virus-mediated NF-kappa B p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta.

Respiratory syncytial virus (RSV) is the etiological agent of acute respiratory diseases, such as bronchiolitis and pneumonia. The exacerbated production of proinflammatory cytokines and chemokines in the airways in response to RSV is an important pillar in the development of these pathologies. As such, a keen understanding of the mechanisms that modulate the inflammatory response during RSV infection is of pivotal importance to developing effective treatment. The NF-kappaB transcription factor is a major regulator of proinflammatory cytokine and chemokine genes. However, RSV-mediated activation of NF-kappaB is far from characterized. We recently demonstrated that aside from the well-characterized IkappaBalpha phosphorylation and degradation, the phosphorylation of p65 at Ser536 is an essential event regulating the RSV-mediated NF-kappaB-dependent promoter transactivation. In the present study, using small interfering RNA and pharmacological inhibitors, we now demonstrate that RSV sensing by the RIG-I cytoplasmic receptor triggers a signaling cascade involving the MAVS and TRAF6 adaptors that ultimately leads to p65ser536 phosphorylation by the IKKbeta kinase. In a previous study, we highlighted a critical role of the NOX2-containing NADPH oxidase enzyme as an upstream regulator of both the IkappaBalphaSer32 and p65Ser536 in human airway epithelial cells. Here, we demonstrate that inhibition of NOX2 significantly decreases IKKbeta activation. Taken together, our data identify a new RIG-I/MAVS/TRAF6/IKKbeta/p65Ser536 pathway placed under the control of NOX2, thus characterizing a novel regulatory pathway involved in NF-kappaB-driven proinflammatory response in the context of RSV infection.

Dual role of NOX2 in respiratory syncytial virus- and sendai virus-induced activation of NF-kappaB in airway epithelial cells.

Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is the most important viral agent of pediatric respiratory tract disease worldwide. Human airway epithelial cells (AEC) are the primary targets of RSV. AEC are responsible for the secretion of a wide spectrum of cytokines and chemokines that are important mediators of the exacerbated airway inflammation triggered by the host in response to RSV infection. NF-kappaB is a key transcription factor responsible for the regulation of cytokine and chemokine gene expression and thus represents a potential therapeutic target. In the present study, we sought to delineate the role of RSV-induced reactive oxygen species in the regulation of the signaling pathways leading to NF-kappaB activation. First, we demonstrate that besides the well-characterized IkappaBalpha-dependent pathway, phosphorylation of p65 at Ser(536) is an essential event regulating NF-kappaB activation in response to RSV in A549. Using antioxidant and RNA-interference strategies, we show that a NADPH oxidase 2 (NOX2)-containing NADPH oxidase is an essential regulator of RSV-induced NF-kappaB activation. Molecular analyses revealed that NOX2 acts upstream of both the phosphorylation of IkappaBalpha at Ser(32) and of p65 at Ser(536) in A549 and normal human bronchial epithelial cells. Similar results were obtained in the context of infection by Sendai virus, thus demonstrating that the newly identified NOX2-dependent NF-kappaB activation pathway is not restricted to RSV among the Paramyxoviridae. These results illustrate a previously unrecognized dual role of NOX2 in the regulation of NF-kappaB in response to RSV and Sendai virus in human AEC.